Diabetes mellitus is an important disease for people nowadays, and the incidence of diabetes has been an upward trend in recent years. Many therapeutic drugs for diabetes have been developed on the basis of mechanisms of onset of diabetes, and have been actually used. For example, an insulin sensitivity enhancer, an α-glycosidase inhibitor, an insulin secretion promoter, insulin preparation, and the like have been used alone or in combination of two or more.
Under such circumstances as described above, a technique has been under development, which is adopted to treat diabetes by activating glycogen synthase, which is a novel mechanism different from those of the aforementioned conventional therapeutic drugs for diabetes. Specifically, biaryloxymethylarenecarboxylic acids have been proposed as compounds capable of activating glycogen synthase (Patent Literatures 1 to 9).
Meanwhile, novel, pharmaceutically active compounds are required to be safe, for example, to have no side effect, in addition to a predetermined effect(s) for the disease treatment. Examining peroxisome proliferator-activated receptors PPARs has been proposed as means for drug safety evaluation (Non Patent Literature 1). This is due to the facts that: in experimental animals such as rats, administering certain drugs leads to hepatomegaly and significantly induces intrahepatic enzymes, and the long-term administration of the drugs causes liver cancer. The changes are characterized by significant proliferation of peroxisomes, which are organelles in the liver. It has been revealed that a receptor PPAR, especially a subfamily PPARα, activated by a peroxisome proliferator (PP) is involved in the mechanism of drug-liver peroxisome proliferation-liver carcinogenesis. This phenomenon has drawn attention at the drug safety evaluation (particularly, carcinogenicity evaluation) in the pharmaceutical drug development stage.